Temsirolimus in Combination With Metformin in Patients With Advanced Cancers

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The goal of this clinical research study is to find the highest tolerable dose of the combination of temsirolimus and metformin that can be given to patients with advanced cancer. The safety of the drug combination will also be studied.

Temsirolimus is designed to block a protein called mTOR (a protein that is thought to cause cancer cells to grow) inside the cancer cell. This may interfere with the growth or spread of cancer cells or possibly kill them.

Metformin was designed to treat patients with diabetes. It may be able to block the protein mTOR and slow the growth of tumors.

This is an investigational study. Temsirolimus is FDA approved and commercially available for the treatment of renal cell carcinoma. Metformin is FDA approved and commercially available for the treatment of diabetes mellitus. The combination of these drugs to treat advanced cancer is investigational.

Up to 104 patients will take part in this study. All will be enrolled at MD Anderson.

Starting dose of Temsirolimus 25 mg by vein weekly. Metformin titrated over 3 weeks at 500 mg by mouth daily. Four weeks of treatment constitute 1 cycle. Cycle one (1) however, will be 6 weeks long to allow for metformin titration.

MTD defined as highest dose studied in which incidence of dose limiting toxicity (DLT) less than 33%. DLTs defined as adverse events (AEs) related to study agents which occur during first cycle of treatment. Toxicity must have possible, probable or definite attribution to study drugs.

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Ages Eligible for Study:

14 Years and older (Child, Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patients with advanced or metastatic cancer that is refractory to standard therapies, who have relapsed after standard therapy, or whose cancers have no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months.

Patients must have evaluable or measurable disease by RECIST criteria.

Patients must be >/= 4 weeks beyond treatment of any chemotherapy, other investigational therapy, hormonal, biological, targeted agents or radiotherapy, and must have recovered to </= grade 1 or previous baseline for each toxicity. Exception: Patients may have received palliative low dose radiotherapy to the limbs 1-4 weeks before this therapy provided pelvis, sternum, scapulae, vertebrae, or skull were not included in the radiotherapy field. Patients who have received non-chemotherapeutic biological agents will need to wait at least 5 half-lives or 4 wks, whichever is shorter, from the last day of treatment. Continuation of hormone replacement therapy is permitted. Stable regimens of hormonal therapy i.e. for prostate cancer (e.g. leuprolide, a GnRH agonist), ovarian, or breast cancer are not exclusionary.

Women of child-bearing potential MUST have a negative serum or urine pregnancy test unless prior hysterectomy or menopause (defined as 12 consecutive months without menstrual activity). Patients should not become pregnant or breastfeed while on this study. Sexually active patients must agree to use contraception prior to study entry, for the duration of study participation, and for 30 days after the last dose

Ability to understand and willingness to sign a written informed consent document.

Patients must be >/= 14 years of age.

Patients in the tumor-specific endometrial carcinoma expansion cohort that have known mutation must be willing to provide consent for biopsies.

Patients with major surgery within 30 days prior to entering the study.

Patients unable to swallow oral medications or with pre-existing gastrointestinal disorders that might interfere with proper absorption of oral drugs.

Patients on drugs that are strong P450 CYP3A4 modifiers. These drugs should be stopped 5 half-lives prior to starting investigational agents with temsirolimus. The strong inducing or inhibiting agents should not restart until 1 week after the end of the study treatment. NOTE: We will allow replacement of steroids (with either prednisone or hydrocortisone) in patients with adrenalectomy.

Patients with a history of any grade of persistent or chronic nausea or vomiting within the last 4 weeks related to prior therapy or disease process.